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目的数据来源于美国中北部癌症治疗组对比Ⅲ期结肠癌患者辅助治疗的随机Ⅲ期临床试验N0147。本研究的目的在于评价吸烟与结肠癌预后、无病生存率(disease free survival,DFS)和肿瘤复发时间(time of tumor recurrence,TTR)相关关系,试图了解其与患者和肿瘤特征异质性的关联。方法 1968名试验参加者完成一份有关吸烟史和其他危险因素的问卷后,将会被随机分配到两个化疗试验组,一组使用静脉滴注氟尿嘧啶、亚叶酸钙、奥沙利铂(FOLFOX)方案,另一组使用FOLFOX联合西妥昔单抗方案。使用Cox模型校正了其他临床或患者因素后,分析评估吸烟史与无病生存率(肿瘤复发或死亡)、及复发时间等主要试验终点的相关关系。未出现终点事件的患者中位随访3.5年。结果与不吸烟患者相比,有吸烟史患者DFS显著较低(3年DFS 70%vs.74%;风险比HR=1.21;95%CI:1.02~1.42)。经过多变量校正,该关联依然存在(HR=1.23;95%CI,1.02~1.49)。BRAF突变状态与该关联显著相关(P=0.03):BRAF野生型结肠癌患者,吸烟者与较低的DFS相关(HR=1.36;95%CI:1.11~1.66);BRAF突变型则无相关(HR=0.80;95%CI:0.50~1.29)。尽管KRAS突变状态产生的相互影响并未达到统计学意义(P=0.07),与KRAS野生型结肠癌相比,吸烟与KRAS突变型患者较差的DFS间存在更强关联[(HR=1.50,95%CI:1.12~2.00)vs.(HR=1.09,95%CI:0.85~1.39)]。在吸烟与TTR的研究分析中,也得出有类似的相关性。结论对于结肠癌患者总体而言,吸烟与较短的DFS及TTR间存在显著关联。而这种不良关联在BRAF野生型和KRAS突变型患者中最为明显。
The data are from the randomized phase III clinical trial N0147 in the North Central United Cancer Society for the adjuvant treatment of patients with stage III colon cancer. The aim of this study was to evaluate the relationship between smoking and the prognosis of colon cancer, the relationship between disease free survival (DFS) and time of tumor recurrence (TTR), and to understand the relationship between smoking and the heterogeneity of patients and tumor characteristics Associated. METHODS: A total of 1968 participants completed a questionnaire on smoking history and other risk factors and were randomized to receive two chemotherapy regimens, one using fluorouracil, leucovorin, oxaliplatin (FOLFOX ) And the other group used FOLFOX in combination with cetuximab. After correlating with other clinical or patient factors using the Cox model, analyzes were performed to assess the association between smoking history and disease-free survival (tumor recurrence or death) and the primary end point of the relapse time. Patients with no endpoint had a median follow-up of 3.5 years. Results Compared with nonsmokers, patients with smoking history had significantly lower DFS (3-year DFS 70% vs 74%; hazard ratio HR = 1.21; 95% CI 1.02-1.42). After multivariate adjustment, the association remained (HR = 1.23; 95% CI, 1.02-1.49). The BRAF mutation status was significantly associated with this association (P = 0.03): patients with BRAF wild-type colon cancer were associated with lower DFS (HR = 1.36; 95% CI: 1.11 to 1.66) and no association with BRAF mutation HR = 0.80; 95% CI: 0.50-1.29). Although the interaction between KRAS mutations did not reach statistical significance (P = 0.07), there was a stronger association between smoking and poor DFS in patients with KRAS mutations than KRAS wild-type colon cancer (HR = 1.50, 95% CI: 1.12-2.00) vs. (HR = 1.09, 95% CI: 0.85-1.39)]. In the study of smoking and TTR analysis, also come to a similar correlation. Conclusion Overall, there was a significant association between smoking and shorter DFS and TTR for patients with colon cancer. This association was most pronounced in BRAF wild-type and KRAS mutant patients.